Most ligands for asymmetric catalysis contain phosphines, including the phosphinoimidazolines found, for example, in U.S. Pat. No. 6,316,620. A common method for construction of these phosphine ligands involves coupling with a secondary phosphine, R2PH.
A fundamental physical property of secondary phosphines is their extreme air sensitivity. Most secondary phosphines will completely oxidize in air within a few minutes to typically undesired secondary phosphine oxides. Because of this problem, there is a long-felt need for improved synthetic procedures for the preparation of secondary phosphines employing a minimum number of synthetic steps and that minimize physical manipulations that may increase the possibility of contact with air. Unfortunately, the prior art methods for preparation of these species suffer from numerous deficiencies.
One prior art method for the preparation of secondary phosphines, which has been proposed to reduce inadvertent oxidation, employs BH3 complexes (Stankevi{hacek over (c)}, M.; Pietrusiewicz, K. M. Synlett 2003, 7, 1012-1016). Unfortunately, in practice, this method has been found to generate undesirable byproducts. Further, there are severe hazards associated with handling BH3 (Reisch, M. Chem. Eng. News 2002, 80 (26), 7).
Another method available for producing secondary phosphines employs lithium aluminum hydride (LAH) (Kapoor, P. N.; Venanzi L. M. Helv. Chim. Acta 1977, 60 (277), 2824-2829). The problem with LAH is that it is also a very hazardous substance to handle. Moreover, in practice, LAH has not been found useful for producing those phosphine ligands that are of particular interest in the art, such as the phosphinoimidazolines.
The reduction of secondary phosphine oxides to secondary phosphines has been accomplished with diphenylsilane (McKinstry, L.; Livinghouse T. Tetrahedron 1994, 50 (21), 6145-6154). Unfortunately, this method requires very high temperatures (i.e., greater than 200° C.). Another method of reducing secondary phosphine oxides uses a combination of trichlorosilane (Cl3SiH) and triethylamine (Elding, L. I.; Kellenberger, B.; Venanzi, L. M. Helv. Chim. Acta 1983, 66 (6), 1676). However, a significant problem with this method is that trichlorosilane is a corrosive reagent, whose extremely low boiling point (31° C.) and low flash point (−13° C.) make it completely unsuitable for typical plant operations.
One of the most common methods for synthesis of secondary phosphine oxides used in industry is a two step process in which an intermediate secondary chlorophosphine is produced (Casalnuovo, A. L; RajanBabu T. V.; Ayers, T. A.; Warren, T. H. J. Am. Chem. Soc. 1994, 116 (22), 9869). A chlorophosphine, an air-sensitive and water-sensitive compound, is first prepared and then isolated. This is carried out with phosphorous trichloride (PCl3), which is a corrosive reagent. High vacuum is employed to fully remove the by-products of this reaction. The chlorophosphine must then be reduced, usually, by LAH, with the hazards associated with using that reagent.
Therefore, there is a need for an improved method for generating secondary phosphines in high yield and purity, without the need to employ hazardous materials.
In U.S. Pat. No. 4,113,783 to Malpass et al., which corresponds to Great Britain Patent No. 1,520,237 to Texas Alkyls, there is described the use of DIBAL-H for the reduction of a tertiary phosphine oxide, triphenylphosphine oxide, to a tertiary phosphine, triphenylphosphine. The patent is specifically directed to triphenylphosphine oxide. No other tertiary phosphine oxides are cited. There is no suggestion for application of DIBAL-H with respect to the reduction of secondary phosphine oxides. Therefore, the usefulness of DIBAL-H in the reduction of secondary phosphine by the present inventor was entirely unexpected.